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Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation

Title: Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation
Authors: Pereira, MG; Voltarelli, VA; Tobias, GC; de Souza, L; Borges, GS; Paixão, AO; de Almeida, NR; Bowen, TS; Demasi, M; Miyabara, EH; Brum, PC
Publisher Information: MDPI
Publication Year: 2022
Collection: White Rose Research Online (Universities of Leeds, Sheffield & York)
Description: Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.
Document Type: article in journal/newspaper
File Description: text
Language: English
ISSN: 2072-6694
Relation: https://eprints.whiterose.ac.uk/id/eprint/182042/6/cancers-14-00028.pdf; Pereira, MG, Voltarelli, VA, Tobias, GC et al. (8 more authors) (2022) Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation. Cancers, 14 (1). 28. ISSN: 2072-6694
Availability: https://eprints.whiterose.ac.uk/id/eprint/182042/
Rights: cc_by_4
Accession Number: edsbas.3479B58E
Database: BASE